Microglial cells, the immune cells of the brain, and the neuroinflammatory process associated, have been
postulated as a critical factor in AD pathogenesis, since the identification of genetic risk factors related to
microglial function. However, the microglial role in the development/progression of AD has not been
determined yet. In this sense, we have previously reported a limited activation and microglial degeneration in
the hippocampus of AD patients in contrast to the proinflammatory view based on findings in amyloidogenic
models. Here, we have further analyzed the functional/phenotypic profile displayed by microglial cells in other
vulnerable brain region of AD patients, the frontal cortex. Immunohistochemistry and image analysis approaches were performed in the frontal cortex of post mortem samples from controls (Braak 0-II) and AD patients (Braak V-VI) including familial cases.
Microglia of Braak V-VI individuals were observed forming clusters and showed, both plaque
(Iba1+/TMEM119+/P2ry12-/CD45high/Trem2+) and inter-plaque (Iba1+/ TMEM119+/P2ry12-/CD45high/Trem2-)
microglial activation, similar that observed in amyloidogenic mice. By contrast, homeostatic and ramified
microglial cells of non-demented Braak II cases presented Iba1+/P2ry12+/TMEM119+/CD45low/Trem2- profile.
Furthermore, different microglial responses were observed between sporadic and familial AD cases.
These different microglial phenotypes associated with AD pathology show the heterogeneity and complexity of
the microglial phenotypes and suggest different functional states of these glial cells in a region-specific
manner. These data need to be considered for better understand the immunological mechanisms underlying
AD progression. Modulating brain inflammatory responses might be a promising avenue to prevent cognitive
dysfunction in AD patients. ISCiii:PI18/01557(AG)-PI18/01556(JV);Junta Andalucia:UMA18-FEDERJA211(AG). All
cofinanced by FEDER funds (European-Union).Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech
